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[Defective generation of NK1.1+ T cells in aly/aly mice associated with thymic architecture]
1Section of Pathology, Hokkaido University, Sapporo, Japan.
It has been reported that positive selection of natural killer antigen 1.1+ (NK1.1+) T cell antigen receptor (TCR) alpha beta+ thymocytes recently identified among CD4+8- and CD4-8- subpopulations is attributable to major histocompatibility complex (MHC) class Ib ligands expressed on bone marrow (BM) derived components in the thymus. This selection pattern is quite different from NK1.1-T cells of main stream. In the present study, we investigated generation of NK1.1+ TCR alpha beta+ cells in the thymus of aly/aly mouse which lacks lymph nodes and Peyer's patches and shows abnormalities of thymic and splenic structure. We found that the proportion of the NK1.1+ TCR alpha beta+ thymocytes was extremely low in these mice as compared with aly/aly+ and normal C57BL/6 mice. Thymic reconstitution by BM cells from aly/aly+ mice which possess a normal population of NK1.1+ TCR alpha beta+ thymocytes did not restore the NK1.1+ TCR alpha beta+ cell population in the thymus of lethally irradiated aly/aly mouse. When deoxy-guanosine (dGuo)-treated fetal thymi from (B6 x B10.G) F1 mice were transplanted to aly/aly mice which had been thymectomized and reconstituted with BM cells of aly/aly mice, normal proportions of the NK1.1+ TCR alpha beta+ thymocytes were observed in the thymus grafts. Furthermore it was demonstrated that NK1.1+ T cells in aly/aly mice were unable to produce efficiently IL-4 upon in vivo stimulation with anti-CD3. These findings demonstrate that the development of NK1.1+ TCR alpha beta+ cells is accomplished under the influence of not only BM derived components but also in intact microenvironment of lymphoid tissues.
It has been reported that positive selection of natural killer antigen 1.1+ (NK1.1+) T cell antigen receptor (TCR) alpha beta+ thymocytes recently identified among CD4+8- and CD4-8- subpopulations is attributable to major histocompatibility complex (MHC) class Ib ligands expressed on bone marrow (BM) derived components in the thymus. This selection pattern is quite different from NK1.1-T cells of main stream. In the present study, we investigated generation of NK1.1+ TCR alpha beta+ cells in the thymus of aly/aly mouse which lacks lymph nodes and Peyer's patches and shows abnormalities of thymic and splenic structure. We found that the proportion of the NK1.1+ TCR alpha beta+ thymocytes was extremely low in these mice as compared with aly/aly+ and normal C57BL/6 mice. Thymic reconstitution by BM cells from aly/aly+ mice which possess a normal population of NK1.1+ TCR alpha beta+ thymocytes did not restore the NK1.1+ TCR alpha beta+ cell population in the thymus of lethally irradiated aly/aly mouse. When deoxy-guanosine (dGuo)-treated fetal thymi from (B6 x B10.G) F1 mice were transplanted to aly/aly mice which had been thymectomized and reconstituted with BM cells of aly/aly mice, normal proportions of the NK1.1+ TCR alpha beta+ thymocytes were observed in the thymus grafts. Furthermore it was demonstrated that NK1.1+ T cells in aly/aly mice were unable to produce efficiently IL-4 upon in vivo stimulation with anti-CD3. These findings demonstrate that the development of NK1.1+ TCR alpha beta+ cells is accomplished under the influence of not only BM derived components but also in intact microenvironment of lymphoid tissues.